Simulation of
membrane proteins in YASARA

The simulation of membrane
proteins is a
sensible task that is complicated by numerous pitfalls. Small errors in
the initial setup can quickly let the membrane fall apart, long before
the self-stabilizing hydrophobic forces can take effect. YASARA
features a complete simulation protocol for membrane proteins, that
takes all the required steps automatically at the touch of a button,
starting from the PDB file of your membrane protein. The following
screenshots summarize the individual steps:

Step 1:
YASARA scans the protein for
secondary structure elements that contain lots of exposed hydrophobic
residues and could be part of a potential transmembrane region. This
example shows bovine rhodopsin, glycosylated and with retinal bound.

Step 2:
Based on the identified
secondary structure elements, the protein is oriented relative to the
membrane, then the final membrane position is determined by scanning
the entire protein surface for the most hydrophobic region.

Step 3:
YASARA shows the suggested
membrane embedding. If required, one can now interactively fine-tune
the membrane position and size.

Step 4:
YASARA builds a membrane of
the required size and with the chosen lipid composition (current
options are phosphatidyl-ethanolamine, -choline, and -serine).

Step 5:
Having cut out exactly the
required number of lipids from the initial membrane, YASARA runs a
compression simulation, where the simulation cell is shrunk
continuously, so that the membrane edges can fuse at the periodic
boundaries.

Step 6:
YASARA embeds the compressed
protein in the membrane, deletes the lipids that bump into the protein,
and then slowly expands the protein during a simulation to fill
the pore, while the lipids adapt. Force field parameters for all
non-standard residues like lipids, ligands and posttranslational
modifications are derived automatically using AutoSMILES.

Step 7:
YASARA fills the cell with
water, carefully avoiding to place water molecules between the lipids.
Then the whole system is energy minimized to remove any conformation
stress from bumps.

Step 8:
YASARA runs an equilibration
simulation lasting 250 ps. During this equilibration phase, the
membrane is artificially stabilized, so that it can adapt to the
protein and the right density without being damaged.